Our long term goal is to apply functional magnetic resonance imaging (fMRl), event-related potentials (ERPs), structured interviews and neuropsychological testing for the prediction of relapse to cocaine use in abstinent cocaine dependent patients. The objectives of this application are to study the effects of cocaine dependence on brain activity and cognition, and test which measures, or combination of measures, best predicts relapse. The rationale behind this research is that the amplitude of the frontal P300 ERP component has been found to be a reliable predictor of relapse to cocaine abuse in abstinent cocaine-dependent patients in treatment. However, the specific neural and cognitive factors that underlie this finding are unknown. FMRI has a spatial resolution that is ideal for imaging the neural architecture of the human brain, and could provide an improved measure of relapse potential. Newly developed methods for performing event-related fMRI will be used to obtain the anatomical locations of neural fields that respond to the same stimuli that generate the P300 ERP component. Recently abstinent cocaine dependent patients will be recruited from local treatment programs after two weeks of abstinence. Abstinence will be verified over a six-month period. Healthy non-drug-dependent volunteers will also be studied. Neuropsychological testing will examine the behavioral consequences of neurophysiological differences found between groups. The combination of ERP, fMRI and neuropsychological methods will provide a precise analysis of changes in brain activity, and their consequences for cognitive task performance, during cocaine withdrawal in humans. It is anticipated that information obtained in the present series of experiments will be useful in understanding the mechanisms of cocaine dependence and relapse, and in improving treatments for this disorder.